Effects of Zinc, Vitamin C and Folic Acid Co-Administration with Artemether-Lumefantrine on Parasitaemia and Oxido-Inflammatory Responses in Plasmodium Berghei-Infected Mice

Authors

  • Abdulmalik Muhammad Danjuma
  • Kamaluddeen Babagana
  • Salihu Ibrahim
  • Jamila Ahmed Mashi Bayero University Kano image/svg+xml

DOI:

https://doi.org/10.33003/fjs-2026-1022-6192

Keywords:

Plasmodium berghei, Artemether-Lumefantrine, Oxidative Stress, Host-Directed Therapy, Zinc, Malaria Pathogenesis

Abstract

Malaria pathogenesis is characterised by severe oxidative stress, systemic inflammation, and profound anaemia, which are often exacerbated by concurrent malnutrition in endemic regions. While artemether-lumefantrine (AL) is highly efficacious in clearing parasites, it does not directly address this collateral damage to the host. This exploratory study evaluated the effects of co-administering Vitamins B9, C, and Zinc with standard AL therapy on oxido-inflammatory responses in Plasmodium berghei-infected Swiss albino mice. Following randomisation (per group), mice were treated with AL alone or in combination with the micronutrients for 4 days. Total parasite burden (Area Under the Curve, AUC), haematological profiles, hepatic antioxidant enzyme activities (Superoxide Dismutase [SOD] and Catalase [CAT]), and systemic C-Reactive Protein (CRP) levels were evaluated. The Kruskal-Wallis analysis of the AUC did not detect a statistically significant difference in parasite clearance kinetics among the treatment groups (). However, micronutrient co-administration significantly improved host biochemical recovery. Zinc-containing regimens markedly elevated hepatic SOD and CAT activities compared to untreated controls, while combinations incorporating Vitamins B9 and C improved Haemoglobin and Red Blood Cell counts and suppressed acute-phase CRP spikes. While the small sample size limits broad clinical inferences, the data suggests these micronutrients may ameliorate malaria-induced oxido-inflammatory damage. Larger pharmacological studies are required to determine specific synergistic mechanisms and clinical safety.

References

Ajayi, A. M., Adebanjo, I. M., & Ademowo, O. G. (2023). Vitamin C-rich juice co-administration with artemether-lumefantrine ameliorates oxido-inflammatory responses in Plasmodium berghei-infected mice. Parasitology Research, 122(8), 1841–1850. https://doi.org/10.1007/s00436-023-07885-5

Akinosoglou, K. S., Solomou, E. E., & Gogos, C. A. (2012). Malaria: a haematological disease. Hematology, 17(2), 106–114. https://doi.org/10.1179/102453312X13221316477336

Barua, P., Chandrasiri, U. P., Beeson, J. G., Dewey, K. G., Maleta, K., Ashorn, P., & Rogerson, S. J. (2018). Effect of nutrient supplementation on the acquisition of humoral immunity to Plasmodium falciparum in young Malawian children NCT01239693 NCT. Malaria Journal, 17(1). https://doi.org/10.1186/s12936-018-2224-6

Buthelezi, M. N., Masia, K. J., Masamba, P., Cedric Simelane, M. B., & Kappo, A. P. (2025). Understanding the interplay of malarial pathogenesis, host immune response and oxidative stress: Implications for disease progression and therapeutic strategies. Aspects of Molecular Medicine, 5, 100082. https://doi.org/10.1016/J.AMOLM.2025.100082

Centers for Disease Control and Prevention. (2024). Micronutrient facts. https://www.cdc.gov/nutrition/features/micronutrient-facts.html

Dawet, A., Barnabas, Dalu, S. 2, & Yakubu. (2023). Food Supplementation Effects on the Parasitaemia and Haematological Parameters of Mice Induced with Plasmodium berghei. Biological and Environmental Sciences Journal for the Tropics, 20(1), 21 – 28. https://www.ajol.info/index.php/bestj/article/view/248518

Kavishe, R. A., Koenderink, J. B., & Alifrangis, M. (2017). Oxidative stress in malaria and artemisinin combination therapy: Pros and cons. FEBS Journal, 284(16), 2579–2591. https://doi.org/10.1111/febs.14097

Kotepui, M., Wilairatana, P., Mala, W., Kotepui, K. U., Masangkay, F. R., & Wangdi, K. (2023). Effects of Daily Zinc Alone or in Combination with Other Nutrient Supplements on the Risk of Malaria Parasitaemia: A Systematic Review and Meta-Analysis of Randomised Controlled Trials. Nutrients, 15(13). https://doi.org/10.3390/nu15132855

Lakkavaram, A., Lundie, R. J., Do, H., Ward, A. C., & de Koning-Ward, T. F. (2020). Acute Plasmodium berghei Mouse Infection Elicits Perturbed Erythropoiesis with Features That Overlap with Anaemia of Chronic Disease. Frontiers in Microbiology, 11. https://doi.org/10.3389/FMICB.2020.00702

Lee, S. R. (2018). Critical Role of Zinc as Either an Antioxidant or a Prooxidant in Cellular Systems. Oxidative Medicine and Cellular Longevity, 2018(1), 9156285. https://doi.org/10.1155/2018/9156285

Ogundeyi, K. J., Ajayi, A. M., Oduyomi, O. J., Adeyemo, S. A., Ologe, M. O., & Ademowo, O. G. (2025). Vitamin C co-administration with artemether-lumefantrine abrogates chronic stress-exacerbated Plasmodium berghei-induced sickness behaviour, inflammatory and oxidative stress responses in mice. Journal of Neuroimmunology, 399, 578518. https://doi.org/10.1016/j.jneuroim.2024.578518

Oyebola, K. M., Ligali, F. C., Owoloye, A. J., Aina, O. O., Alo, Y. M., Erinwusi, B., Olufemi, M. J., & Salako, B. L. (2024). Assessing the therapeutic efficacy of artemether-lumefantrine for uncomplicated malaria in Lagos, Nigeria: a comprehensive study on treatment response and resistance markers. Malaria Journal, 23(1). https://doi.org/10.1186/s12936-024-05088-6

Palmer, A. C., Bedsaul-Fryer, J. R., & Stephensen, C. B. (2023). Interactions of nutrition and infection: The role of micronutrient deficiencies in the immune response to pathogens and implications for child health. Annual Review of Nutrition, 43(1), 47-75. https://doi.org/10.1146/annurev-nutr-062122-120000

Percário, S., Moreira, D. R., Gomes, B. A. Q., Ferreira, M. E. S., Gonçalves, A. C. M., Laurindo, P. S. O. C., Vilhena, T. C., Dolabela, M. F., & Green, M. D. (2012). Oxidative Stress in Malaria. International Journal of Molecular Sciences, 13(12), 16346. https://doi.org/10.3390/IJMS131216346

Sakzabre, D., Asiamah, E. A., Akorsu, E. E., Abaka-Yawson, A., Dika, N. D., Kwasie, D. A., Ativi, E., Tseyiboe, C., & Osei, G. Y. (2020). Haematological Profile of Adults with Malaria Parasitaemia Visiting the Volta Regional Hospital, Ghana. Advances in Hematology, 2020, 9369758. https://doi.org/10.1155/2020/9369758

Salcedo-Sora, J. E., Ochong, E., Beveridge, S., Johnson, D., Nzila, A., Biagini, G. A., Stocks, P. A., O’Neill, P. M., Krishna, S., Bray, P. G., & Ward, S. A. (2011). The molecular basis of folate salvage in plasmodium falciparum: Characterization of two folate transporters. Journal of Biological Chemistry, 286(52), 44659–44668. https://doi.org/10.1074/jbc.M111.286054

Sarki, A., Pukuma, M. S., Yoriyo, K. P., Kunihya, I. Z., Hafizu, M. S., Kolawole, A. A., Haruna, M. Y., & Ali, R. (2019). Study on malaria infection in pregnant women attending primary health care centres in Gombe metropolis, Gombe State, Northeast, Nigeria. FUDMA Journal of Sciences, 3(4), 115–119. https://www.bing.com/ck/a?!&&p=8e598f98cfe24b42f49eee45f68b7a7279fccd334a5426ae27dd452453aca1a5JmltdHM9MTc5MDk4NTYwMA&ptn=3&ver=2&hsh=4&fclid=2293a7cc-5565-6492-1dbf-b19754de65e3&psq=FUDMA+Journal+of+Sciences+(FJS)+article+on+malaria&u=a1aHR0cHM6Ly9manMuZnVkdXRzaW5tYS5lZHUubmcvaW5kZXgucGhwL2Zqcy9hcnRpY2xlL2Rvd25sb2FkLzE2MjgvMTI4OS8zMjI4

Tola, F. S. (2024). The concept of folic acid supplementation and its role in prevention of neural tube defect among pregnant women: PRISMA. Medicine, 103(19), e38154. https://doi.org/10.1097/MD.0000000000038154

Vasquez, M., Zuniga, M., & Rodriguez, A. (2021). Oxidative Stress and Pathogenesis in Malaria. Frontiers in Cellular and Infection Microbiology, 11, 768182. https://doi.org/10.3389/FCIMB.2021.768182

World Health Organization. (2024). Malaria. https://www.who.int/news-room/fact-sheets/detail/malaria

Wong, C. P., Beaver, L. M., & Ho, E. (2025). Protective role of dietary zinc on DNA damage, oxidative stress, and metal toxicity. Frontiers in Molecular Biosciences, 12, 1618318. https://doi.org/10.3389/FMOLB.2025.1618318/REFERENCE

Haematological profiles following 4-day therapeutic intervention

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Published

05-11-2026

How to Cite

Danjuma, A. M., Babagana, K., Ibrahim, S., & Mashi, J. A. (2026). Effects of Zinc, Vitamin C and Folic Acid Co-Administration with Artemether-Lumefantrine on Parasitaemia and Oxido-Inflammatory Responses in Plasmodium Berghei-Infected Mice. FUDMA Journal of Sciences, 10(22), 345-351. https://doi.org/10.33003/fjs-2026-1022-6192

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